For treatment of drug dependencies and associated toxicities, previous work by our group has demonstrated the potential for drug development in three major areas: low affinity NMDA antagonists, strychnine insensitive glycine site antagonists, and benztropine. Recent preclinical findings and anecdotal clinical reports have suggested the potential for ibogaine to treat a host of chemical dependencies. We have demonstrated, for the first time, a plausible mechanism of action of ibogaine in the interruption of drug dependencies. Electrophysiological, neurochemical, and behavioral pharmacological data indicate that ibogaine functions as a low affinity blocker of the NMDA associated ion channel. Current efforts are focused on the discovery of other compounds in this class that do not have the ancillary side effect profile of ibogaine (tremor, ataxia, and phencyclidine like effects). Work on the glycine site has provided the first definitive evidence that low efficacy partial agonists, shown to block the development and expression of behavioral and toxicological sequelae of abused drugs, produce subjective effects (predicted in preclinical models) that are driven by agonist binding to that site; these effects are distinct from the sedative and psychotomimetic effects produced by other drugs which produce functional blockade of NMDA associated neurotransmission. We and others have postulated that the adjunct anti Parkinson drug, benztropine (Cogentin), may be a suitable candidate for clinical investigation as a psychomotor stimulant therapy. Our data suggests that behavioral and subjective effect profiles of benztropine can be distinguished from those of classical antimuscarinics and also distinct from those of dopamine uptake blockers like cocaine. Our results further substantiate the predicted safety of benztropine in clinical trials for adjunct treatment of psychomotor stimulant abuse.